CHLORPROTHIXENE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C18H18ClNS
Molecular Weight	315.86
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN(C)CC\C=C1\C2=CC=CC=C2SC3=C1C=C(Cl)C=C3

InChI

InChIKey=WSPOMRSOLSGNFJ-AUWJEWJLSA-N

InChI=1S/C18H18ClNS/c1-20(2)11-5-7-14-15-6-3-4-8-17(15)21-18-10-9-13(19)12-16(14)18/h3-4,6-10,12H,5,11H2,1-2H3/b14-7-

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/14065076
Curator's Comment: description was created based on several sources, including, http://www.mentalmeds.org/prescription_meds/Truxal.html, https://www.ncbi.nlm.nih.gov/pubmed/24071734

Chlorprothixene (Taractan, Tarasan, Truxal) is a thioxanthine derivative developed by Lundbeck for the treatment of psychotic disorders. The drug exerts its activity by binding to and inhibiting serotonin receptors, dopamine receptors, muscarinic acetylcholine receptor, histamine H1 receptor and alpha1-adrenergic receptor.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Dopamine D1 receptor 101 Target ID: CHEMBL2056 Sources: http://www.mentalmeds.org/prescription_meds/Truxal.html	Antagonist 2778	18.0 nM [Ki]
Serotonin (5-HT) receptor 34 Target ID: CHEMBL2096904 Sources: http://www.mentalmeds.org/prescription_meds/Truxal.html	Antagonist 2778
Adrenergic receptor alpha-1 169 Target ID: CHEMBL2094251 Sources: http://www.mentalmeds.org/prescription_meds/Truxal.html	Antagonist 2778
Histamine H1 receptor 315 Target ID: P35367 Gene ID: 3269.0 Gene Symbol: HRH1 Target Organism: Homo sapiens (Human) Sources: http://www.mentalmeds.org/prescription_meds/Truxal.html	Antagonist 2778	3.75 nM [Ki]
Muscarinic acetylcholine receptor 160 Target ID: CHEMBL2094109 Sources: http://www.mentalmeds.org/prescription_meds/Truxal.html	Antagonist 2778
D(2) dopamine receptor 58 Target ID: P14416 Gene ID: 1813.0 Gene Symbol: DRD2 Target Organism: Homo sapiens (Human) Sources: http://www.mentalmeds.org/prescription_meds/Truxal.html	Antagonist 2778	3.4 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Psychosis 16 Sources: https://www.medikamente-per-klick.de/images/ecommerce/08/48/08481217_2011-10_de_o.pdf	Primary		Approved 8429	TRUXAL Approved Use To treat psychosis.

C_max

Value	Dose	Co-administered	Analyte	Population
11 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1140253/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:		CHLORPROTHIXENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
187 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1140253/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:		CHLORPROTHIXENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
8.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1140253/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:		CHLORPROTHIXENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

Doses

Dose	Population	Adverse events
1800 mg 1 times / day multiple, oral (max) Highest studied dose Dose: 1800 mg, 1 times / day Route: oral Route: multiple Dose: 1800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1314010	unhealthy, 25-49 years n = 7 Health Status: unhealthy Age Group: 25-49 years Sex: M+F Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/1314010	Disc. AE: Polyneuropathy... AEs leading to discontinuation/dose reduction: Polyneuropathy (7 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/1314010

AEs

AE	Significance	Dose	Population
Polyneuropathy	7 patients Disc. AE	1800 mg 1 times / day multiple, oral (max) Highest studied dose Dose: 1800 mg, 1 times / day Route: oral Route: multiple Dose: 1800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1314010	unhealthy, 25-49 years n = 7 Health Status: unhealthy Age Group: 25-49 years Sex: M+F Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/1314010

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
		substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BCRP 699 MRP2 383 P-gp 1461 OCT1 512 OATP2B1 123 OATP1B1 788 OATP1B3 706 BSEP 402	P-gp 1537

Drug as perpetrator

Target	Modality	Activity
BSEP 403	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw2MDIwIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDkwOCJ9fQ%3D%3D	yes [IC50 27.47 uM]
BCRP 773	inhibitor 3277 Sources: https://link.springer.com/article/10.1007/s11095-009-9896-0, https://www.sciencedirect.com/science/article/pii/S0928098717301343	yes [IC50 42 uM]
MRP2 475	inhibitor 3277 Sources: https://link.springer.com/article/10.1007/s11095-009-9896-0, https://www.sciencedirect.com/science/article/pii/S0928098717301343	yes [IC50 74 uM]
OCT1 543	inhibitor 3277 Sources: https://pubs.acs.org/doi/10.1021/jm8003152	yes [IC50 77.8 uM]
OATP1B1 803	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNjk3NjY4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDkwOCJ9fQ%3D%3D	yes [Inhibition 20 uM]
OATP1B3 715	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMTIxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDkwOCJ9fQ%3D%3D	yes [Inhibition 20 uM]
OATP2B1 126	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMTI0IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDkwOCJ9fQ%3D%3D	yes [Inhibition 20 uM]
P-gp 1650	inhibitor 3277 Sources: https://www.sciencedirect.com/science/article/pii/S0928098717301343	yes [Ki 31.4 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12438524/	no
CYP2D6 1217	substrate 3367 Sources: https://link.springer.com/chapter/10.1007%2F978-3-642-25761-2_10	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:3651	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3651
eMolecules	1986150	https://www.emolecules.com/cgi-bin/more?vid=1986150

PubMed

Title	Date	PubMed
The antibacterial effect of selected phenothiazines and thioxanthenes on slow-growing mycobacteria.	1986 Dec	3105243
A repurposing approach identifies off-patent drugs with fungicidal cryptococcal activity, a common structural chemotype, and pharmacological properties relevant to the treatment of cryptococcosis.	2013 Feb	23243064

Sample Use Guides

In Vivo Use Guide

The usual adult dose is 15-100 mg (mild to moderate symptoms) or 100-400 mg (severe symptoms).

Route of Administration: Oral

In Vitro Use Guide

70 uM of cis-chlorprothixene produced approximately 50% inhibition of axonal transport measured in vitro in spinal nerves of the bullfrog.

Name

Type

Language

CHLORPROTHIXENE

Official Name

English

RO-40403

Code

English

N-714RO 4-0403

Code

English

N-714

Code

English

CHLORPROTHIXENE [MI]

Common Name

English

CHLORPROTHIXENE [ORANGE BOOK]

Common Name

English

CHLORPROTHIXENE [MART.]

Common Name

English

CHLORPROTHIXENE [JAN]

Common Name

English

RO-4-0403

Code

English

chlorprothixene [INN]

Common Name

English

Chlorprothixene [WHO-DD]

Common Name

English

TARACTAN

Brand Name

English

1-PROPANAMINE, 3-(2-CHLORO-9H-THIOXANTHEN-9-YLIDENE)-N,N-DIMETHYL-, (Z)-

Systematic Name

English

CHLORPROTHIXENE [VANDF]

Common Name

English

CHLORPROTHIXENE [USAN]

Common Name

English

NSC-18720

Code

English

CHLORPROTHIXENE [HSDB]

Common Name

English

(Z)-2-CHLORO-N,N-DIMETHYLTHIOXANTHENE-.DELTA.(SUP 9,.GAMMA.)-PROPYLAMINE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29710